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Biomedical subjects

Maria Eyman

Publications and source records attributed to Maria Eyman.

5 recordsLinked to original sources

Synaptosomal protein synthesis is selectively modulated by learning.

Synaptosomes from rat brain have long been used to investigate the properties of synaptic protein synthesis. Comparable analyses have now been made in adult male rats trained for a two-way active avoidance task to examine the hypothesis of its direct participation in brain plastic events. Using Ficoll-purified synaptosomes from neocortex, hippocampus and cerebellum, our data indicate that the capacity of synaptosomal protein synthesis and the specific activity of newly synthesized proteins were not different in trained rats in comparison with home-caged control rats. On the other hand, the synthesis of two proteins of 66.5 kDa and 87.6 kDa separated by SDS-PAGE and analyzed by quantitative densitometry was selectively enhanced in trained rats. In addition, the synthesis of the 66.5 kDa protein, but not of the 87.6 kDa protein, correlated with avoidances and escapes and inversely correlated with freezings in the neocortex, while in the cerebellum it correlated with avoidances and escapes. The data demonstrate the participation of synaptic protein synthesis in plastic events of behaving rats, and the selective, region-specific modulation of the synthesis of a synaptic 66.5 kDa protein by the newly acquired avoidance response and by the reprogramming of innate neural circuits subserving escape and freezing responses.

Animals↗

Nerve terminals of squid photoreceptor neurons contain a heterogeneous population of mRNAs and translate a transfected reporter mRNA.

It is now well established that the distal structural/functional domains of the neuron contain 2a diverse population of mRNAs that program the local synthesis of protein. However, there is still a paucity of information on the composition and function of these mRNA populations in the adult nervous system. To generate empirically, hypotheses regarding the function of the local protein synthetic system, we have compared the mRNAs present in the squid giant axon and its parental cell bodies using differential mRNA display as an unbiased screen. The results of this screen facilitated the identification of 31 mRNAs that encoded cytoskeletal proteins, translation factors, ribosomal proteins, molecular motors, metabolic enzymes, nuclear-encoded mitochondrial mRNAs, and a molecular chaperone. Results of cell fractionation and RT-PCR analyses established that several of these mRNAs were present in polysomes present in the presynaptic nerve terminal of photoreceptor neurons, indicating that these mRNAs were being actively translated. Findings derived from in vitro transfection studies established that these isolated nerve terminals had the ability to translate a heterologous reporter mRNA. Based upon these data, it is hypothesized that the local protein synthetic system plays an important role in the maintenance/remodelling of the cytoarchitecture of the axon and nerve terminal, maintenance of the axon transport and mRNA translation systems, as well as contributing to the viability and function of the local mitochondria.

Amino Acid Sequence↗

Squid photoreceptor terminals synthesize calexcitin, a learning related protein.

Nerve endings of squid photoreceptor neurons generate large synaptosomes upon homogenization of the optic lobe. Using several independent methods, these presynaptic structures have been shown to synthesize a wealth of soluble, cytoskeletal and nuclear encoded mitochondrial proteins, and to account for essentially all the translation activity of the synaptosomal fraction. We are now presenting evidence that calexcitin, a learning related, Ca(2+)-binding protein of the B photoreceptors of Hermissenda crassicornis (a mollusk), is synthesized and subjected to post-translational modifications in the squid photoreceptor terminals. In view of the essential role of presynaptic protein synthesis in long-term memory formation in Aplysia, our data suggest that a comparable role may be played by calexcitin synthesized in the squid photoreceptor terminals.

Animals↗

Altered midbrain dopaminergic neurotransmission during development in an animal model of ADHD.

To understand the onset and the molecular mechanisms triggering dopaminergic (DA) dysregulation in Attention-Deficit Hyperactivity Disorder (ADHD), we have used the Spontaneously Hypertensive Rats (SHR), the most widely studied animal model for this disease. We have studied the pattern of expression of specific genes involved in DA neuron differentiation, survival and function during postnatal (P) development of the ventral midbrain in SHR males. Our results show that tyrosine hydroxylase and DA transporter gene expression are significantly and transiently reduced in the SHR midbrain during the first month of postnatal development, although with a different kinetic. The other genes analyzed do not show significant variation between SHR and control rats. In addition, high-affinity DA uptake activity is significantly reduced in synaptosomes obtained from the striatum of 1-month-old SHR, when compared to controls. Our data suggest that down-regulation of DA neurotransmission occurs in the midbrain of SHR in a developmentally regulated temporal window during postnatal development, thus strengthening the hypodopaminergic hypothesis in the pathogenesis of ADHD.

Animals↗